PROJECT ABSTRACT With sepsis screening and increased compliance with evidence based, guidelines-driven standard operating procedures for early diagnosis and treatment of sepsis in surgical intensive care unit (ICU) patients, early mortality has been dramatically reduced and late-onset fulminant multiple organ failure has virtually disappeared. A new phenotype of chronic critical illness (CCI), however, has emerged in surgical ICU patients characterized by prolonged ICU stays, recurrent nosocomial infections, poor wound healing, progressive cachexia and manageable organ dysfunctions. We have coined the term persistent inflammation, immunosuppression and catabolism syndrome (PICS) to reflect the pathophysiologic hallmarks of this growing epidemic. Many of these patients (especially the elderly) are discharged to long-term acute care facilities where they often suffer an indolent death. We hypothesize that CCI characterized by morbid long-term outcomes is now a predominant clinical trajectory of surgical ICU patients who survive sepsis. The overall objective of Project #1 is to characterize the epidemiology of CCI in surgical ICU patients who develop sepsis and to determine its long-term consequences. The challenge is to return those surgical ICU patients who survive sepsis to a functional, productive life, and to reduce their burden to the healthcare system and to society through early interventions. We need to identify early, however, which patients are at highest risk for morbid long-term outcomes and might benefit from novel interventions. Project #1's main functions will be the following: * Define the epidemiology and long-term consequences of sepsis in surgical ICU patients. Clearly, there is a compelling need to better understand the long-term consequences of sepsis in surgical ICU patients, especially those who progress into CCI who are at high risk for PICS. * Identify clinical indices and biomarkers that can predict CCI in surgical ICU patients early (within 48 hours) after sepsis. These prediction models could help provide insight into underlying pathophysiology and design entry criteria in future trials. * Identify clinical indices and biomarkers on day 14 in patients with CCI after sepsis that predict morbid outcome (defined as death or full functional dependency at 1 year). These findings could be used to gain insight into underlying pathophysiology by comparing novel biomarkers at earlier time points in patients at highest risk for morbid long-term outcomes versus those patients at lowest risk. A CCI score could then be developed as a composite endpoint in future interventional trials. To accomplish the above goals, Project #1 will perform, over 5 years, a single-site, prospective, longitudinal study of 400 adult surgery and trauma ICU patients who develop sepsis.